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- Title
Human skeletal muscle insulin receptor substrate-1. Characterization of the cDNA, gene, and chromosomal localization.
- Authors
Araki, Eiichi; Xiao-Jian Sun; Yitao Zhang; Yang-Feng, Teresa L.; White, Moris F.; Kahn, C. Ronald; Araki, E; Sun, X J; Haag, B L 3rd; Chuang, L M; Zhang, Y; Yang-Feng, T L; White, M F; Kahn, C R
- Abstract
Insulin receptor substrate-1 is a major substrate of insulin receptor Tyr kinase. We have now cloned the IRS-1 cDNA from human skeletal muscle, one of the most important target tissues of insulin action, localized and cloned the human IRS-1 gene, and studied the expression of the protein in Chinese hamster ovary cells. Human IRS-1 cDNA encodes a 1242 amino acid sequence that is 88% identical with rat liver IRS-1. The 14 potential Tyr phosphorylation sites include 6 Tyr-Met-X-Met motifs and 3 Tyr-X-X-Met motifs that are completely conserved in human IRS-1. Human IRS-1 has > 50 possible Ser/Thr phosphorylation sites and one potential ATP-binding site close to the NH2-terminal. The human IRS-1 gene contains the entire 5'-untranslated region and protein coding region in a single exon and was localized on chromosome 2 q36-37 by in situ hybridization. By Northern blot analysis, IRS-1 mRNA is rare and consists of two species of 6.9 and 6 kilobase. By using quantitative polymerase chain reaction after reverse transcription of total RNA from human fetal tissues, IRS-1 mRNA could be identified in all tissues. When human IRS-1 cDNA was expressed in Chinese hamster ovary cells, the protein migrated between 170,000-180,000 M(r) in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and was rapidly Tyr phosphorylated upon insulin stimulation. Thus, IRS-1 is widely expressed and highly conserved across species and tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
- Publication
Diabetes, 1993, Vol 42, Issue 7, p1041
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diab.42.7.1041